Intracellular survival of Candida glabrata in phagocytes
Although Candida glabrata is an emerging pathogen with increasing importance in hospital-associated (nosocomial) systemic infections, little is known about the basic pathogenicity mechanisms and interplay of this fungus with the host immune system. During infection, phagocytes are key players of the innate immune response to C. glabrata. However, although C. glabrata is efficiently phagocytosed, the fungus not only survives phagocytosis, but even replicates within monocyte-derived macrophages. Therefore it is likely that this fungus employs immune evasion strategies to survive in its human host. Indeed, our data indicate that C. glabrata modifies phagosome maturation, residing in a non-acidic late endosomal compartment of macrophages.
In my PhD project I aim to identify factors or activities involved in fungal inhibition of phagosome maturation and further characterize the intracellular compartment, in which the fungus resides. Therefore I want to elucidate the presence of stage specific markers such as the proton pump vATPase, responsible for acidification of C. glabrata containing phagosomes, or the lysosomal tracer dextran, which is also planned to be used to identify mutants lacking the ability to arrest phagosome maturation. Furthermore the isolation of C. glabrata containing phagosomes in cooperation with Dr. Norbert Reiling/Borstel/Germany followed by proteomics is intended.
A related subproject will focus on the interaction of C. glabrata with a second type of phagocytic cells of the innate immune response: polymorphonuclear leucocytes (PMNs), which act as the main defense mechanism against the related opportunistic pathogen C. albicans. A selection of mutants which have shown attenuated survival in macrophages will be analyzed for their interaction facing PMNs.
(2018) Metals in Fungal Virulence. FEMS Microbiol Rev 42(1),
(2017) The Fungal Pathogen Candida glabrata Does Not Depend on Surface Ferric Reductases for Iron Acquisition. Front Microbiol 8, 1055.
(2016) A Novel Hybrid Iron Regulation Network Combines Features from Pathogenic and Nonpathogenic Yeasts. MBio 7(5),
(2014) Identification of Candida glabrata genes involved in pH modulation and modification of the phagosomal environment in macrophages. PLoS One 9(5), e96015.
(2014) Immune evasion, stress resistance, and efficient nutrient acquisition are crucial for intracellular survival of Candida glabrata within macrophages. Eukaryot Cell 13(1), 170-183.
Start of PhD
October 1, 2011
December 13, 2017